Table 2.

Mouse models of LPL dysfunction and hyperlipidemia.

Mouse model	Description	The effect on LPL	Phenotype	Reference(s)
cld/cld	Autosomal recessive mutation in mouse chromosome 17, a naturally occurring mutation	The loss of LPL (and hepatic lipase) activity	Develop severe hyperlipidemia, milky serum, ischemia, cyanosis soon after birth, and died within 36–48 hours after birth.	[15]
Lmf1 −/−	Global LMF1 deficiency by gene trap mutagenesis	The loss of LPL (and hepatic lipase) activity	Recapitulating the phenotypes of cld/cld mice.	[17]
Sel1LAdipoq-cre	Adipocyte-specific SEL1L deficiency using adiponectin promoter-driven Cre	ER retention of LPL aggregates, and reduced LPL secretion	Postprandial hyperlipidemia and resistant to HFD-induced obesity with ectopic lipid accumulation in the liver upon HFD.	[22]
Angptl4-Tg	Whole body overexpression of mouse ANGPTL4	Significantly reduced postheparin LPL activity	Severe hypertriglyceridemia and chylomicronemia in fasted state; retention of chylomicrons in plasma after 24-hour fasting; reduced fat mass; increased lipolysis in adipose tissue; mild insulin resistance	[83, 84]
Hepatocyte Angptl4-Tg	Hepatocytespecific overexpression of human ANGPTL4 driven by the ApoE promoter	Mildly reduced post-heparin LPL activity	Increased plasma triglycerides and cholesterol under fed condition.	[85]
Angptl3 and Angptl8	Overexpression of mouse ANGPTL3 by adenoviral infection or human ANGPTL8 by hydrodynamic DNA delivery	Not tested	Increased plasma triglyceride levels	[93], [92]
Gpihbp1 −/−	Global deficiency in GPIHBP1	Mis-localization of LPL in the interstitial space	Early onset of severe chylomicronemia within 4–14 weeks of age	[34, 38]
Apoa5−/−; Apoa5 knockdown	Global knockout of Apo-AV; 60% knockdown of hepatic Apo-AV protein using targeted antisense oligonucleotide treatment	Decreased plasma LPL activity	Significantly increased plasma triglyceride levels; reduced plasma lipid clearance rate	[49, 50]
Apoc1 overexpression	Hemizygous expression of the human apoc1 gene;	Not tested	Markedly increased plasma triglyceride levels; mildly increased plasma cholesterol levels	[55]
Apoc3 overexpression	Overexpression of human apo-CIII	Not tested	Markedly increased plasma triglyceride levels; reduced clearance of VLDL triglycerides	[54]

Abbreviation: HFD: high-fat diet; Tg: Transgenic.